Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT3VZ24)

• DTT Name: NIMA-related kinase 2 (NEK2)
• Synonyms: Serine/threonine-protein kinase Nek2; NimA-related protein kinase 2; NimA-like protein kinase 1; Never in mitosis A-related kinase 2; NLK1; NEK2A; HSPK 21
• Gene Name: NEK2
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Kinase
• UniProt ID: NEK2_HUMAN
• TTD ID: T49102
• EC Number: EC 2.7.11.1
• Sequence:
  MPSRAEDYEVLYTIGTGSYGRCQKIRRKSDGKILVWKELDYGSMTEAEKQMLVSEVNLLR
  ELKHPNIVRYYDRIIDRTNTTLYIVMEYCEGGDLASVITKGTKERQYLDEEFVLRVMTQL
  TLALKECHRRSDGGHTVLHRDLKPANVFLDGKQNVKLGDFGLARILNHDTSFAKTFVGTP
  YYMSPEQMNRMSYNEKSDIWSLGCLLYELCALMPPFTAFSQKELAGKIREGKFRRIPYRY
  SDELNEIITRMLNLKDYHRPSVEEILENPLIADLVADEQRRNLERRGRQLGEPEKSQDSS
  PVLSELKLKEIQLQERERALKAREERLEQKEQELCVRERLAEDKLARAENLLKNYSLLKE
  RKFLSLASNPELLNLPSSVIKKKVHFSGESKENIMRSENSESQLTSKSKCKDLKKRLHAA
  QLRAQALSDIEKNYQLKSRQILGMR
• Function: Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly. NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis. Involved in the regulation of centrosome disjunction. Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells.
• Reactome Pathway:
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)
  Loss of Nlp from mitotic centrosomes (R-HSA-380259)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)
  Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  AURKA Activation by TPX2 (R-HSA-8854518)
  APC-Cdc20 mediated degradation of Nek2A (R-HSA-179409)

Molecular Interaction Atlas (MIA) of This DTT

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK579289A	DMJXHU8	Discovery agent	N.A.	Investigative	[1]
PMID20936789C31	DMUGWO6	Discovery agent	N.A.	Investigative	[2]
PMID21627121C2	DMQHAIK	Discovery agent	N.A.	Investigative	[3]

References

• [1] Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding. Bioorg Med Chem Lett. 2009 Mar 15;19(6):1694-7.
• [2] Aminopyrazine inhibitors binding to an unusual inactive conformation of the mitotic kinase Nek2: SAR and structural characterization. J Med Chem. 2010 Nov 11;53(21):7682-98.
• [3] Irreversible Nek2 kinase inhibitors with cellular activity. J Med Chem. 2011 Jun 23;54(12):4133-46.